We have investigated the subcellular localization and effect of overexpressing neuregulin in hippocampal neurons. Our previous studies suggest that neuregulin exists in clusters in hippocampal neurons. We examined whether these neuregulin clusters associate with specific subcellular regions, and whether the pattern of distribution is regulated during neuronal development. We stained neuorns transfected with a plasmid expressing neuregulin with antibodies against synaptic proteins. We did not detect significant colocalization of neuregulin with synaptic markers. Treatments that enhance or decrease neuronal activities did not affect the subcellular localization of neuregulin. Overexpression of neuregulin altered the morphological development of synapses. This finding indicates that neuregulin regulates synapse development. Therefore neuregulin might contribute to developmental deficits of neural networks underlying schizophrenia.